One of the major methods for investigating the mechanisms of action of morphine has been to determine its effects upon brain putative neurotransmitters. It is hoped that some day human drug abuse can be controlled by treatment with compounds that can specifically block the reinforcing effects of the drug being abused without themselves producing physical dependence or undesirable side effects. Until the underlying physical mechanisms of the reinforcing properties of these abused drugs are known, the development and screening of specific antagonists of these effects will be difficult. This research proposal is for a series of studies that will systematically investigate the neurochemical correlates of intravenous morphine self-administration. The levels and turnover of nine putative neurotransmitters will be concurrently measured in individual brain areas of rats self-administering morphine. By using appropriate control groups, it will be possible to determine the neurochemical correlates of the reinforcing properties of morphine. The neuroanatomical and neurotransmitter systems important in maintaining morphine self-administration will be further characterized by using chemical and electrolytic lesions in minute brain areas and simultaneously assessing the effects upon drug-taking behavior and putative neurotransmitter systems. The effects of narcotic antagonists upon this "morphine reinforcement system" will then be determined. Once the neurochemical mechanisms of this drug-taking behavior and its localization in the CNS are known, the development and screening of specific antagonists of these reinforcing properties will be possible.